The objectives of the present study are to : (1) Characterize, localize and investigate the synthesis and regulation of ACTH, LPH (lipotropin) and their fragments that are found in the brain. (2) Investigate the possible role of neurotransmitter substances, hypophysiotrophic factors and other small peptides in directly effecting ACTH and LPH secretion from various pituitary lobes and to determine if such secretion always occurs in parallel. (3) Identify factors involved in regulation of the circadian pattern of plasma corticosteroid concentrations (CPOHCS) seen in animals maintained on altered feeding schedules. (4) Identify subgroups of patients with Cushing's Disease (CD) and Nelson's Syndrome (ND) that may represent CNS vs. pituitary etiologies so as to provide a guide to appropiate therapy. METHODS: Several species will be studied: (adult, fetal) (rat, sheep, cow, monkey, human) (1) ACTH 1-39, ACTH 18-39, ACTH 1-13, beta-LPH, beta-MSH, beta-LPH 61-91 will be characterized by a combination of immunoassay, bioassay, immunocytochemistry, gel filtration and gel electrophoresis in control animals and following hypophysectomy, pituitary stalk section, arcuate nucleus lesions, corticosteroid administration, adrenalectomy and stress. (2) Pars distalis, intermedia and nervosa cells will be incubated with test substances (singly and in combination) and concentrations of ACTH, LPH and fragments thereof in cells and media determined. In other experiments the pituitary response to the effluent of hypothalamic fragments superfused with these test substances will be assessed. (3) The effect of fornix section, ventromedial nucleus lesions and light-dark phase shift on the "altered feeding" CPOHCS will be studied. (4) The pre-treatment sleep EEG, plasma ACTH and/or cortisol response to TRF, and sellar polytomography in patients with CD and NS will be correlated with the type of response obtained with treatment with cyproheptadine to see if these parameters can be used as prognostic factors.